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The combination of anti-depressant and narcotic might be the best treatment option for neuropathic pain. Researchers in Denmark recently released a comprehensive study to determine the best treatment for neuropathic pain. They analyzed the combined results of 174 research reports on the efficacy of multiple and varied treatment options. Researchers discovered that the combination of tricyclic antidepressants and opioids may be first-line therapies for a number of neuropathic conditions.

In this Danish review, a second tier of agents (NNTs 3-6) include SNRIs, tramadol, and lidocaine patch. Cannabinoids (eg, marijuana and related agents) were considered in some of the research trials; however, while there was a favorable level of safety compared with placebo, moderate efficacy was only evident for central pain (NNT 3.4) and mixed neuropathies (NNT 8.3).

The study breaks down the efficacy of pharmacological agents over a wide range of neuropathies (see the link at the end of this post). However, In terms of safety as indicated by NNH values, both opioids (NNH 17.1) and tricyclic antidepressants (TCAs) (NNH 15.9) exhibited reasonably favorable profiles.

2 Replies |Watch This Discussion | Report This| Share this:Research Update for Neuropathic Pain TreatmentsThe combination of anti-depressant and narcotic might be the best treatment option for neuropathic pain. Researchers in Denmark recently released a comprehensive study to determine the best treatment for neuropathic pain. They analyzed the combined results of 174 research reports on the efficacy of multiple and varied treatment options. Researchers discovered that the combination of tricyclic antidepressants and opioids may be first-line therapies for a number of neuropathic conditions.

In this Danish review, a second tier of agents (NNTs 3-6) include SNRIs, tramadol, and lidocaine patch. Cannabinoids (eg, marijuana and related agents) were considered in some of the research trials; however, while there was a favorable level of safety compared with placebo, moderate efficacy was only evident for central pain (NNT 3.4) and mixed neuropathies (NNT 8.3).

The study breaks down the efficacy of pharmacological agents over a wide range of neuropathies (see the link at the end of this post). However, In terms of safety as indicated by NNH values, both opioids (NNH 17.1) and tricyclic antidepressants (TCAs) (NNH 15.9) exhibited reasonably favorable profiles.

Hello Charles, thanks for sharing the article and link to that website; I love how the articles are to the point and not filled with too much fluff that the average Joe has difficulty in interpreting.

I have a question for you though:I do believe that the combination of anti-depressants and opioids are more efficacious in treating those with chronic pain; however, do you believe that if an individual requires an increase in pain medications (i.e. for achieved tolerance), that there should be a subsequent change (or increase) in anti-depressant dosages?

Also, I am concerned about my meds and I'm wondering if you could help me out. I've been on 100mcg Fentanyl for 2 months. 2 months prior, 75 mcgs. (all doses are prescribed at 48 hr intervals). My patch reaches its best delivery between hours of 12 through 36; outside of this time frame I'm struggling with increased pain (even more than I had on lower doses of these opiods), therefore I rely heavily on BT med's. Is it possible that my body has become so used to the medication that when the levels are off; resulting in stronger pain signals?? More directly, is this medication tricking my brain signals to believe my pain is really that bad?

I am not certain if this teeters on hyper-algesia or not, but I'm feeling like this is very distinct.

Also, on the advice you have given on the pain board repeatedly, I consulted my doctor about the possibility of rotating my BT meds (now roxicodone at 15 mgs/4x day) in order to get better pain relief. He has told me on numerous occasions that I'm on a very strong dose as it is and there isn't much out there to change to. He said that "patients who usually need that may have issues of hyper-algesia, but (I) don't fit that profile".

Thanks for your time, and I hope to hear from you soon! I truly hope you are doing well, Sincerely, Brennan

I have a question for you though:I do believe that the combination of anti-depressants and opioids are more efficacious in treating those with chronic pain; however, do you believe that if an individual requires an increase in pain medications (i.e. for achieved tolerance), that there should be a subsequent change (or increase) in anti-depressant dosages?

Also, I am concerned about my meds and I'm wondering if you could help me out. I've been on 100mcg Fentanyl for 2 months. 2 months prior, 75 mcgs. (all doses are prescribed at 48 hr intervals). My patch reaches its best delivery between hours of 12 through 36; outside of this time frame I'm struggling with increased pain (even more than I had on lower doses of these opiods), therefore I rely heavily on BT med's. Is it possible that my body has become so used to the medication that when the levels are off; resulting in stronger pain signals?? More directly, is this medication tricking my brain signals to believe my pain is really that bad?

I am not certain if this teeters on hyper-algesia or not, but I'm feeling like this is very distinct.

Also, on the advice you have given on the pain board repeatedly, I consulted my doctor about the possibility of rotating my BT meds (now roxicodone at 15 mgs/4x day) in order to get better pain relief. He has told me on numerous occasions that I'm on a very strong dose as it is and there isn't much out there to change to. He said that "patients who usually need that may have issues of hyper-algesia, but (I) don't fit that profile".

Thanks for your time, and I hope to hear from you soon! I truly hope you are doing well, Sincerely, Brennan

Hi BrenBren. I understand your situation completely. Fentanyl is the most powerful pain medication available. Once you reach the maximum dose and still become tolerant, you must turn to your BT meds (because rotating to a different primary narcotic will result in far more pain). Believe me. I've been there. You could ask your doctor about wearing two patches. The worst that happen is he'll say, "No." But, research has established that people can live with very high dosages of narcotics without damage. The trick is to increase the dosage very gradually. Still, most physicians fear respiratory depression with more than one 100 mcg patch at a time. Some terminal cancer patients wear more than one 100 mcg patch at a time. I've heard of some people who wear one 100 mcg patch and another 15 mcg or 25 mcg patch simultaneously.

Some people (like me and maybe you) have an unusually-high tolerance for pain medications (CNS depressants). I've always required more than a normal amount of pain medication to achieve the expected result. The same applies to alcohol. When I was in college, I could drink everyone under the table and still appear sober. Some of us have a genetic predisposition to CNS-depressant tolerance. But, I don't know if saying that will convince your doctor to allow you to wear two patches.

I have had good results with Oxycodone for BT medication. But, even then, I periodically become tolerant. When that occurs, I rotate to Marinol for a couple of months. Marinol's active ingredient is THC (yes, the same ingredient in marijuana). Research reveals that THC binds with opioid receptors in the brain, just like opioids (narcotics). Frankly, Marinol does not relieve pain as well as Oxycodone, for me. But, it is an adequate substitute until my Oxycodone tolerance has been dissipated. Some people say that smoking it is far more efficacious than acquiring the drug via a capsule. Certainly, it enters the bloodstream mush faster via pulmonary ingestion. And, there are additional chemicals that enter the bloodstream via pulmonary ingestion. But, smoking can damage tissues, is potentially carcinogeous and the added chemicals can be dangerous to the heart. In the end, ingesting THC via the stomach results in a similar plasma level (although it takes longer to work), plus it seems to last longer.

Will your doctor allow you to rotate to Marinol? Maybe not. It is off label for pain (it was designed to treat the nausea and weight loss associated with chemotherapy). My doctor is exceedingly liberal about allowing me to do the research and try new ideas. Most doctors are not so generous.

In the end, you and I are at the same place. When you reach the strongest safe dosage of the strongest pain medications, there is nothing comparable for rotation. In essence, we must "grin and bear it." Perhaps in the not too distant future, something stronger than Fentanyl will arrive. You can also look at it from the other side. Many chronic pain patients suffer needlessly because their physicians are afraid to prescribe Fentanyl in the first place. To be honest, without Fentanyl, I would likely decide not to live. So, we're fortunate to have Fentanyl, even when we are tolerant to it. If you ever doubt the efficacy of Fentany, feel free to rotate to something different. I did. You do not want to know how that felt.

BrenBren, you likely know that hyperalgesia is exceedingly rare. Most physicians will practice a lifetime and never see it. If you had it, you would have noticed a significant increase in pain upon starting the medication, not long after that time. I would bet the mortgage (or what little is left of it) that you do NOT have hyperalgesia. You have severe chronic pain and tolerance, just like me.

Best of luck to you. And, know that I am out there researching every day. If I see something new, I'll post it here. Feel free to do the same.

Thanks for your Reply!

Report This| Share this:Research Update for Neuropathic Pain TreatmentsHi BrenBren. I understand your situation completely. Fentanyl is the most powerful pain medication available. Once you reach the maximum dose and still become tolerant, you must turn to your BT meds (because rotating to a different primary narcotic will result in far more pain). Believe me. I've been there. You could ask your doctor about wearing two patches. The worst that happen is he'll say, "No." But, research has established that people can live with very high dosages of narcotics without damage. The trick is to increase the dosage very gradually. Still, most physicians fear respiratory depression with more than one 100 mcg patch at a time. Some terminal cancer patients wear more than one 100 mcg patch at a time. I've heard of some people who wear one 100 mcg patch and another 15 mcg or 25 mcg patch simultaneously.

Some people (like me and maybe you) have an unusually-high tolerance for pain medications (CNS depressants). I've always required more than a normal amount of pain medication to achieve the expected result. The same applies to alcohol. When I was in college, I could drink everyone under the table and still appear sober. Some of us have a genetic predisposition to CNS-depressant tolerance. But, I don't know if saying that will convince your doctor to allow you to wear two patches.

I have had good results with Oxycodone for BT medication. But, even then, I periodically become tolerant. When that occurs, I rotate to Marinol for a couple of months. Marinol's active ingredient is THC (yes, the same ingredient in marijuana). Research reveals that THC binds with opioid receptors in the brain, just like opioids (narcotics). Frankly, Marinol does not relieve pain as well as Oxycodone, for me. But, it is an adequate substitute until my Oxycodone tolerance has been dissipated. Some people say that smoking it is far more efficacious than acquiring the drug via a capsule. Certainly, it enters the bloodstream mush faster via pulmonary ingestion. And, there are additional chemicals that enter the bloodstream via pulmonary ingestion. But, smoking can damage tissues, is potentially carcinogeous and the added chemicals can be dangerous to the heart. In the end, ingesting THC via the stomach results in a similar plasma level (although it takes longer to work), plus it seems to last longer.

Will your doctor allow you to rotate to Marinol? Maybe not. It is off label for pain (it was designed to treat the nausea and weight loss associated with chemotherapy). My doctor is exceedingly liberal about allowing me to do the research and try new ideas. Most doctors are not so generous.

In the end, you and I are at the same place. When you reach the strongest safe dosage of the strongest pain medications, there is nothing comparable for rotation. In essence, we must "grin and bear it." Perhaps in the not too distant future, something stronger than Fentanyl will arrive. You can also look at it from the other side. Many chronic pain patients suffer needlessly because their physicians are afraid to prescribe Fentanyl in the first place. To be honest, without Fentanyl, I would likely decide not to live. So, we're fortunate to have Fentanyl, even when we are tolerant to it. If you ever doubt the efficacy of Fentany, feel free to rotate to something different. I did. You do not want to know how that felt.

BrenBren, you likely know that hyperalgesia is exceedingly rare. Most physicians will practice a lifetime and never see it. If you had it, you would have noticed a significant increase in pain upon starting the medication, not long after that time. I would bet the mortgage (or what little is left of it) that you do NOT have hyperalgesia. You have severe chronic pain and tolerance, just like me.

Best of luck to you. And, know that I am out there researching every day. If I see something new, I'll post it here. Feel free to do the same.

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